Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis.
Cell Metab
; 33(6): 1124-1136.e5, 2021 06 01.
Article
en En
| MEDLINE
| ID: mdl-33811820
ABSTRACT
Cellular senescence is a stress or damage response that causes a permanent proliferative arrest and secretion of numerous factors with potent biological activities. This senescence-associated secretory phenotype (SASP) has been characterized largely for secreted proteins that participate in embryogenesis, wound healing, inflammation, and many age-related pathologies. By contrast, lipid components of the SASP are understudied. We show that senescent cells activate the biosynthesis of several oxylipins that promote segments of the SASP and reinforce the proliferative arrest. Notably, senescent cells synthesize and accumulate an unstudied intracellular prostaglandin, 1a,1b-dihomo-15-deoxy-delta-12,14-prostaglandin J2. Released 15-deoxy-delta-12,14-prostaglandin J2 is a biomarker of senolysis in culture and in vivo. This and other prostaglandin D2-related lipids promote the senescence arrest and SASP by activating RAS signaling. These data identify an important aspect of cellular senescence and a method to detect senolysis.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Oxilipinas
/
Fenotipo Secretor Asociado a la Senescencia
/
Senoterapéuticos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2021
Tipo del documento:
Article